PB1877: EFFECTS OF VENETOCLAX-BASED COMBINATIONS FOR THE TREATMENT OF NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA IN CLINICAL SETTINGS
Authors: Young Seob Park, Min Kyoung Kim
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Recently, several therapeutic agents have been developed for the treatment of older adults or medically unfit patients with acute myeloid leukemia (AML). In such patients, venetoclax plus azacitidine combination therapy has shown superior overall survival (OS) and complete response (CR) rate over azacitidine alone. In addition, because its toxicity is tolerable, venetoclax has become one of the main therapeutic agents for AML. Aims: In this study, we aimed to evaluate the treatment outcomes and toxicity of venetoclax-based combinations in newly diagnosed elderly or unfit patients with AML in a clinical setting and compared the treatment response when using azacitidine and decitabine in combination. In addition, we compared the OS of patients given a reduced dose of venetoclax with CYP3A inhibitors with that of patients given the original dose of venetoclax(400 mg) without CYP3A inhibitors. Methods: We retrospectively reviewed the clinical data of 22 untreated AML patients who were ineligible for intensive chemotherapy and received venetoclax plus hypomethylating agent/low dose cytarabine as a frontline treatment at four medical centers between March 2020 and December 2022. The primary end point of this study was the rate of composite CR (CR and CR with incomplete hematologic recovery [CRi]). The other end points were overall response (CR, CRi, morphologic leukemia-free state [MLFS], and partial remission [PR]), OS, toxicities and 30-day mortality. Response to therapy was evaluated according to European leukemia net (ELN)-2017 Criteria. Results: Of the 22 patients enrolled, azacytidine (Aza) was used in 10 patients (45.5%), decitabine (Dec) in 11 patients (50%), and LDAC in 1 patient (4.5%). 12 of the 22 patients (54.5%) were female. The median age of all patients was 75.5 years (range 51-86). According to 2017 ELN criteria, 36.4% (n=8) were at adverse risk and 18.2% (n=4) were at favorable risk. Patients received a median of two cycles of chemotherapy (range, 1–18). Among 15 assessable patients, best responses were CR (n=3), CRi (n=4), MLFS (n=3), and PR (n=2), and two patients showed progressive disease. The composite CR rate was 46.7%, and the overall response rate was 80%. Median time to response was 0.92 months (range, 0.82–3.84). During a median follow-up of 3.1 months (range 0.8-23.7), the median OS was 5.29 months (95% confidence interval, 0.8 to 9.8) for all patients. There was no difference in OS between the patients receiving Aza and Dec (6.1 months vs 5.3 months, respectively, p=0.406). There was no significant difference in the OS of patients receiving reduced dose+CYP3A inhibitor (n=13) and original dose of venetoclax (n=9) (Not reached vs 5.3 months, respectively, p=0.782). The most frequently reported hematologic adverse events of Grade 3 or higher included febrile neutropenia (72.7%), neutropenia (86.4%), and thrombocytopenia (86.4%). Notable infectious adverse events were sepsis (22.7%) and pneumonia (31.8%). The percentages of patients who discontinued chemotherapy owing to adverse event was 31.8% (n=7). Of these seven patients, only one patient discontinued the drug due to a hematologic adverse event. Mortality at 30 days was 4.5% (n=1) in this study. Summary/Conclusion: This is a real-world study in which very elderly, frail patients were enrolled, compared to the VIALE-A trial. Through the composite CR rate (46.7%) and overall response rate (80%), deep hematological responses and manageable toxicities were shown despite the use of venetoclax for these patients. Although the number of enrolled patients was small, there was no significant difference in OS on administrating concomitant HMAs (Aza vs Dec) and OS on administrating venetoclax (reduced dose vs full dose).Keywords: Acute myeloid leukemia, Venetoclax, Treatment-related mortality